Radionuclides such as F-18, N-13, O-15, and C-11 can be produced by a variety of techniques and for a variety of purposes. An increasingly important radionuclide is the F-18 (18F−) ion, which has a half-life of 109.8 minutes. F-18 is typically produced by operating a cyclotron to proton-bombard stable O-18 enriched water (H218O), according to the nuclear reaction 18O(p,n)18F. After bombardment, the F-18 can be recovered from the water. For at least the past two decades, F-18 has been produced for use in the chemical synthesis of the radiopharmaceutical fluorodeoxyglucose (2-fluoro-2-deoxy-D-glucose, or FDG), a radioactive sugar. FDG is used in positron emission tomography (PET) scanning. PET is utilized in nuclear medicine as a metabolic imaging modality employed to diagnose, stage, and restage several cancer types. These cancer types include those for which the Medicare program currently provides reimbursement for treatment thereof, such as lung (non-small cell/SPN), colorectal, melanoma, lymphoma, head and neck (excluding brain and thyroid), esophageal, and breast malignancies. When FDG is administered to a patient, typically by intravenous means, the F-18 label decays through the emission of positrons. The positrons collide with electrons and are annihilated via matter-antimatter interaction to produce gamma rays. A PET scanning device can detect these gamma rays and generate a diagnostically viable image useful for planning surgery, chemotherapy, or radiotherapy treatment.
It is estimated that the cost to provide a typical FDG dose is about 30% of the cost to perform a PET scan, and the cost to produce F-18 is about 66% of the cost to provide the FDG dose derived therefrom. Thus, according to this estimate, the cyclotron operation represents about 20% of the cost of the PET scan. If the cost of F-18 could be lowered by a factor of two, the cost of PET scans would be reduced by 10%. Considering that about 350,000 PET scans are performed per year, this cost reduction could potentially result in annual savings of tens of millions of dollars. Thus, any improvement in F-18 production techniques that results in greater efficiency or otherwise lowers costs is highly desirable and the subject of ongoing research efforts.
At the present time, about half of the accelerators such as cyclotrons employed in the production of F-18 are located at commercial distribution centers, and the other half are located in hospitals. The full production potential of these accelerators is not realized, at least in part because current target system technology cannot dissipate the heat that would be produced were the full available beam current to be used. About one of every 2,000 protons stopping in the target water produces the desired nuclear reaction, and the rest of the protons simply deposit heat. It is this heat that limits the amount of radioactive product that can be produced in a given amount of time. State-of-the-art target water volumes are typically about 1–3 cm3, and can typically handle up to about 500 W of beam power. In a few cases, up to 800 W of beam power have been attained. Commercially available cyclotrons capable of providing 10–20 MeV proton beam energy, are actually capable of delivering two or three times the beam power that their respective conventional targets are able to safely dissipate. Future cyclotrons may be capable of four times the power of current machines. It is proposed herein that, in comparison to conventional targets, if target system technology could be developed so as to tolerate increased beam power by a factor of ten to fifteen, the production of F-18 could be increased by up to an order of magnitude or more, and the above-estimated cost savings would be magnified.
In conventional batch boiling water target systems, a target volume includes a metal window on its front side in alignment with a proton beam source, and typically is filled with target water from the top thereof. The beam power applied to such targets is limited by the fact that above a critical beam power limit, boiling in the target volume will cause a large reduction in density, due to the appearance of a large number of vapor bubbles, which reduces the effective length of the target chamber thus moving the region of highest proton absorption into the chamber's rear wall. As a result, the target structure will receive the higher levels of particles instead of the target fluid, the target structure will be heated and not all of the target fluid will provide radioactive product. To avoid this consequence, it is proposed herein according to at least one embodiment to move the fluid out from the particle beam, at or below the point of vaporization, and conduct the fluid to a heat exchanger to extract the unwanted heat. In this manner, the only limit to the beam power allowed to impinge on the fluid would be the rate of fluid flow through the beam chamber and the ability of the heat exchanger to extract the unwanted entropy.
An opposite approach to reducing the cost of F-18 production is to use a low-energy (8 MeV), high current (100–150 mA) proton beam, as disclosed in U.S. Pat. No. 5,917,874. A cooled target volume is connected to a top conduit and a bottom conduit. A front side of the target is defined by a thin (6 μm) foil window aligned with the proton beam generated by a cyclotron. The window is supported by a perforated grid for protection against the high pressure and heat resulting from the proton beam. The target volume is sized to enable its entire contents to be irradiated. A sample of O-18 enriched water to be irradiated is injected into the target volume through the top conduit. The resulting F-18 is discharged through the bottom conduit by supplying helium through the top conduit. Such target systems as disclosed in U.S. Pat. No. 5,917,874, deliberately designed for use in conjunction with a low-power beam source, cannot take advantage of the full power available from commercially available high-energy beam sources.
As an alternative approach to the use of batch or static targets in which the target material remains in the target throughout the irradiation step, a recirculating target can be used in which the target liquid carrying the target material is circulated through the target, through a loop, and back into the target. A recirculating target is disclosed in U.S. Patent Application Pub. No. 2003/0007588. The purpose of this design is to remove F-18 continuously by slowly circulating the target fluid through an in-line trap. This avoids contaminating the irradiated fluid by not recovering the fluid in a batch via plastic tubing. In this disclosure, the target system employs a single-piston pump set to a flow rate of 5 ml/min. The liquid outputted from the target is cooled by running it through a coil that is suspended in ambient air, resulting in only a minor amount of heat removal. The cyclotron provided with this system was rated at 16.5 MeV and 75 μA, meaning that the beam power potentially available was about 1.23 kW. However, in practice the system was operated at only about 0.64 kW. It is believed that this system would not be suitable for beam powers in the range of about 1.5 kW or greater, as the single-piston pump and coil would not prevent the target liquid from boiling above about 0.64 kW.
It would therefore be advantageous to provide a recirculative target device and associated radionuclide production apparatus and method that are compatible with the full range of beam power commercially available currently and in the future, and that are characterized by improved efficiencies, performance and radionuclide yield.